|Title||Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Grba, DN, Hirst, J|
|Journal||Nat Struct Mol Biol|
|Date Published||2020 Aug 03|
Mitochondrial complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from ubiquinone reduction by NADH to drive protons across the energy-transducing inner membrane. Recent cryo-EM analyses of mammalian and yeast complex I have revolutionized structural and mechanistic knowledge and defined structures in different functional states. Here, we describe a 2.7-Å-resolution structure of the 42-subunit complex I from the yeast Yarrowia lipolytica containing 275 structured water molecules. We identify a proton-relay pathway for ubiquinone reduction and water molecules that connect mechanistically crucial elements and constitute proton-translocation pathways through the membrane. By comparison with known structures, we deconvolute structural changes governing the mammalian 'deactive transition' (relevant to ischemia-reperfusion injury) and their effects on the ubiquinone-binding site and a connected cavity in ND1. Our structure thus provides important insights into catalysis by this enigmatic respiratory machine.
|Alternate Journal||Nat. Struct. Mol. Biol.|